# Retrograde signaling and the modulation of short-term plasticity at an auditory synapse

> **NIH NIH F32** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $12,468

## Abstract

Project Summary
The nerve terminals of auditory neurons are responsible for the efficient release and recycling of synaptic
vesicles that enable the secure chemical transmission that underlies auditory perception. The fidelity and
modulation of these synaptic events is important in the superior olivary complex (SOC) of the mammalian
brainstem, which is involved in sound source localization. The calyx of Held nerve terminal is an integral
component of this afferent projection pathway, which projects from the globular bushy cells (GBCs) of the
anteroventral cochlear nucleus (aVCN) and synapses onto the principal cells (PCs) of the medial nucleus of the
trapezoid bodies (MNTB). The calyx of Held-MNTB synapse contributes specifically to the transduction of
interaural intensity differences from sound cues initiated at each cochlea. Although it is well-established that
synaptic efficacy changes at an acute timescale in response to previous activity, the underlying mechanisms
regulating short-term modifications in synaptic strength in the auditory brainstem require further investigation.
The work proposed here seeks to understand how retrograde signaling regulates presynaptic short-term
plasticity (STP) at the mouse calyx of Held-MNTB synapse. A hallmark of this synapse is the ability to maintain
synaptic fidelity during high frequency transmission (i.e. at frequencies ≥ 800 Hz in vivo), a range at which
conventional synaptic boutons cannot reliably fire. The nano-domain regulation of local ionic environments is a
well-accepted signaling mechanism of synaptic transmission. Because of the high-fidelity necessary for the
functional output of this synapse, extracellular synaptic K+ accumulation is likely higher at auditory synapses
than traditional synaptic boutons during persistent spiking activity. We hypothesize that local microenvironments
of K+ in the femtoliter volume of the synaptic space contributes to the activity-dependent regulation of STP at the
presynaptic nerve terminal. The aims of this project are to 1) determine the homeostatic regulation of extracellular
K+ during synaptic activity; 2) determine how postsynaptic depolarization regulates cytosolic Ca2+ concentration
in the mature presynaptic nerve terminal; 3) determine how retrograde signaling modulates presynaptic STP. To
pursue these aims, a combination of mouse genetics, synaptic electrophysiology and Ca2+ imaging approaches
will be used. The results of this grant proposal will provide insights on the intrinsic modulation of synaptic strength
and plasticity at developing and mature synapses of the auditory system. This will lead to a better understanding
of healthy human spatial hearing and reveal potential synaptic mechanisms for treating hearing disorders.

## Key facts

- **NIH application ID:** 9982312
- **Project number:** 5F32DC017644-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Brendan Lujan
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $12,468
- **Award type:** 5
- **Project period:** 2018-08-01 → 2020-09-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982312

## Citation

> US National Institutes of Health, RePORTER application 9982312, Retrograde signaling and the modulation of short-term plasticity at an auditory synapse (5F32DC017644-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9982312. Licensed CC0.

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